Hutchmed upbeat on preclinical data for novel cancer therapy
By Josh White
Date: Thursday 23 Oct 2025
(Sharecast News) - Hutchmed China reported preclinical data on Thurdsay, showing strong anti-tumour activity for its novel cancer therapy HMPL-A251, the first investigational drug to emerge from the company's proprietary Antibody-Targeted Therapy Conjugate (ATTC) platform.
The AIM-traded firm presented the findings this week at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.
It described HMPL-A251 as a first-in-class HER2-targeted conjugate that combines a potent and selective PI3K/PIKK inhibitor payload with a humanised anti-HER2 antibody via a cleavable linker.
Hutchmed said it was designed to address limitations of traditional toxin-based antibody-drug conjugates and standalone PAM-pathway inhibitors by enhancing tumour specificity while reducing systemic toxicity.
Preclinical studies demonstrated that HMPL-A251 achieved robust anti-tumour efficacy in vitro and in vivo across a range of HER2-positive and HER2-low models.
The compound showed strong HER2-dependent activity, inducing tumour cell apoptosis through inhibition of the PI3K/AKT/mTOR signalling pathway.
It also displayed synergistic and bystander killing effects, maintaining efficacy even in models with PAM-pathway alterations.
In comparative studies, HMPL-A251 achieved efficacy comparable to or greater than trastuzumab deruxtecan (T-DXd), a leading HER2-directed ADC, at equivalent doses.
Unlike toxin-based ADCs, Hutchmed said the ATTC approach uses pathway-modulating payloads designed for safer, long-term administration.
It said HMPL-A251 achieved potent tumour regression with minimal free-payload exposure in plasma - measured at less than one part per 500,000 - suggesting an improved safety profile.
"We are excited to share the progress of HMPL-A251, the first candidate from our ATTC platform," said Dr Michael Shi, Hutchmed's head of research and development and chief medical officer.
"It represents a potentially significant leap forward in addressing the limitations of toxin-based ADCs and the narrow therapeutic window of systemic PAM inhibitors.
"By combining selective PI3K/PIKK inhibition with precise HER2 targeting, HMPL-A251 achieves potent antitumor effects while maintaining a favourable safety profile."
He added that the results "underscore its potential to redefine treatment for a wide spectrum of cancers," noting that Hutchmed planned to advance HMPL-A251 and other ATTC candidates into clinical development.
The company said global clinical trials for HMPL-A251 were expected to begin around the end of 2025, with additional investigational new drug (IND) filings for other ATTC candidates planned in 2026.
At 1000 BST, shares in Hutchmed China were up 0.88% at 230p.
Reporting by Josh White for Sharecast.com.
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